Cancer is one of the leading causes of death in advanced countries. Numerous chemotherapeutic agents have been developed in the past 50 years for the purpose of treating cancer. The majority of chemotherapeutic agents are classified into alkylating agents, metabolic antagonists, anthracyclines, plant alkaloids, topoisomerase inhibitors or antitumor agents. All of these pharmaceutical agents exert therapeutic effects through a mechanism that functions in some form by having an effect on cell division or DNA synthesis.
The efficacy of a specific chemotherapeutic agent varies according to the type of cancer, the patient and the elapsed time in an individual patient. Cancer cells that have been exposed to a chemotherapeutic agent may develop tolerance to that chemotherapeutic agent and frequently similarly develop cross-tolerance to a plurality of other chemotherapeutic agents as well. Moreover, depending on the mechanism of these chemotherapeutic agents, there are many cases in which the dosage or usage of a chemotherapeutic agent is restricted in order to control adverse side effects brought about as a result of cell damage to normal cells caused by these chemotherapeutic agents.
Development has been proceeded in recent years on molecular target drugs that target molecules specifically expressed in cancer cells as an alternative to conventional chemotherapeutic agents. The appearance of these molecular target drugs has enabled to treat cancer and thus contributes to patient QOL by avoiding the characteristic adverse side effects of conventional chemotherapeutic agents. These molecular target drugs include small molecule pharmaceutical agents as well as large molecule pharmaceutical agents such as antibodies. Although therapeutic antibodies target molecules expressed on the cell surface, in addition to offering the advantage of low toxicity since antibody molecules per se are molecules that are intrinsically present in the body, therapeutic antibodies also offer the advantage of demonstrating therapeutic effects by specifically damaging target cells by a mechanism of action other than that of a small molecule therapeutic agent, such as cytotoxicity mediated by an effector function, and numerous therapeutic antibodies have been commercially marketed in recent years.
LAMP5 (also known as BAD-LAMP, C20orf103, UNC-43 or NCBI reference sequence: NM 012261 and NM 001199897) is a type I transmembrane protein that was discovered by the group of Philippe Pierre et al. to be a lysosome-associated membrane protein-like (LAMP-like) protein expressed in mouse brain ([NPL 1]). The same group later reported that LAMP5 is also expressed in plasmacytoid dendritic cells (pDCs) in humans (NPL 2). pDCs are cells that are involved in natural immunity, and rapidly produce type I interferons after having detected a viral infection (NPL 3). In addition, although pDCs are mainly present in lymph nodes, small amounts have also been detected in peripheral blood. Although a cell surface marker for detecting pDCs is required to efficiently analyze pDCs present in peripheral blood, there are few specific markers available (NPL 4).
LAMP5 has an intracellular sorting signal sequence on the C-terminal thereof, and is localized in intracellular granules designated as endoplasmic reticulum-Golgi intermediate compartments (ERGIC) within pDCs (NPL 2). On the other hand, LAMP-like proteins are typically localized in lysosomes and endosomes and some of those are also expressed on the cell membrane (NPLs 5 and 6). LAMP1 and LAMP2 have been shown to be expressed on the cell membrane in cancer cell lines in analyses using FACS (NPL 7). However, it is not known as to whether or not LAMP5 is expressed on the cell surface in a state that enables it to be targeted by a molecular target drug.